tbuckley/cabot-search huggingface dataset:
Biomarker-directed therapy in black and white men with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Clara Hwang, Nicholas Henderson, Frank Cameron Cackowski, Amanda Pilling, Albert Jang, Shoshana Rothstein, Matthew Labriola, Joseph J. Park, Alyssa Ghose, Mehmet Asim Bilen, Deepak Kilari, Abhishek Tripathi, Rohan Garje, Vadim S Koshkin, Michael Thomas Schweizer, Andrew J. Armstrong, Rana R. McKay, Tanya B. Dorff, Ajjai Shivaram Alva, Pedro C. Barata
Journal: Journal of Clinical Oncology (2022)

5013 Background: Black men have been underrepresented in large-scale molecular prostate cancer (PC) surveys, despite having higher PC incidence and mortality. Since molecular profiling to guide the use of targeted agents is increasingly important in mCRPC, we compared precision medicine data and utilization in a cohort of black and white men with mCRPC. Methods: The PROMISE precision medicine database is an academic collaboration to compile clinical and genomic data from men with PC. All patients have had germline and/or somatic genetic testing performed. Eligibility criteria for this analysis included a diagnosis of mCRPC with available race and biomarker data. The primary outcome was the proportion of non-Hispanic black (NHB) and non-Hispanic white (NHW) men with actionable molecular data, defined as the presence of mismatch repair deficiency (MMRd/MSI-H), homologous recombination repair deficiency (HRRd), tumor mutational burden (TMB) ≥ 10 mut/MB, or AR-V7. Secondary outcomes included the proportion of NHB and NHW men with other alterations, the type and timing of genomic testing performed, and the use of targeted therapy. Results: A total of 962 mCRPC patients (21.2% NHB; 78.8% NHW) met inclusion criteria of 1619 in the overall database. Median age (NHB/NHW) was 61/63; 77.5/68.8% had Gleason 8-10; 52.5/56.7% presented with de novo metastatic disease (33.8/29.9% LN, 36.2/32.2% bone and 8.3/6.1% viscera). The median time from diagnosis to first molecular result was 56.3 mo for NHB v 58.7 mo for NHW (p = 0.45). Use of blood-based molecular testing was more common in NHB men (48.7% v 36.4%, p &lt; 0.001). Overall, 32.8% of NHB men harbored actionable molecular data compared to 30.3% of NHW men (Table). MMRd/MSI-H was more common in NHB men (9.1 v 4.9%, p = 0.04). Other than PTEN (12.7/23.8% NHB/NHW, p = 0.0001), no significant differences were seen in the 15 most frequently mutated genes, including TP53, AR, CDK12, RB1, and PIK3CA. Tumor suppressor co-mutations (PTEN/TP53/RB1) were found in 13.1% of NHB and 18.0% NHW (p = 0.13). Delivery of targeted therapy was reported in 19.6% of NHB and 23.7% of NHW men (p = 0.25) after a median of 2 CRPC lines. Median OS from development of mCRPC was 41.5 mo (95% CI, 34.7-51.3) and 44.7 mo (95% CI, 41.1-51.5) for NHB and NHW men, respectively (p = 0.14). Conclusions: In a real-world mCRPC molecular profiling cohort, we found similar overall rates of actionable molecular alterations in NHB and NHW men, but higher rates of MMRd/MSI-H and lower frequency of PTEN alterations in NHB men. We did not find differences in delivery of targeted therapy. [Table: see text]
Bone mineral density (BMD) deficits in adult survivors of childhood cancer: Attributable risks and long-term consequences.
Authors: Chelsea Goodliffe Goodenough, Jessica L Baedke, Nan Li, Tara M. Brinkman, Carmen Louise Wilson, Angela M. Delaney, Hiroto Inaba, Karen L Clark, Gregory T. Armstrong, Aimee C. Talleur, Ching-Hon Pui, Daniel M. Green, Thomas E. Merchant, Deo Kumar Srivastava, Yutaka Yasui, Melissa M. Hudson, Leslie L. Robison, Sue C. Kaste, Kirsten K. Ness, Wassim Chemaitilly
Journal: Journal of Clinical Oncology (2022)

e22021 Background: Survivors of childhood cancer are at risk for BMD deficits. Contributions of treatment, physical and lifestyle factors to overall risk are unknown as are long-term consequences of moderate and severe deficits. Methods: BMD deficits were evaluated in 3919 five-year childhood cancer survivors in the St. Jude Lifetime Cohort (median age 31.7 [range 18.0-69.9] years, 52.6% male, 80.4% non-Hispanic White) using lumbar quantitative computed tomography and classified by age- and sex-specific Z-scores as moderate (&lt;-1SD) or severe deficit (&lt;-2SD). Multivariable logistic regression estimated odds ratios (OR), risk factor attributable fractions (AF), and associations between BMD deficits and long-term outcomes (social/functional outcomes, fracture, mortality). Results: BMD deficits were moderate in 21.7% (95% CI 20.4%-23.0%) and severe in 6.9% (95% CI 6.1%-7.7%) of survivors. Risk factors for moderate deficit included age 5-9 years at diagnosis (OR 1.63, 95% CI 1.31-2.03), &gt;20Gy cranial radiotherapy (OR 1.75, 95% CI 1.41-2.18), &gt;3240 mg/m 2 glucocorticoids (OR 1.34, 95% CI 1.09-1.66), and smoking (OR 1.55, 95% CI 1.27-1.90). AF were 7.2%, 0.7%, 5.9%, and 6.1% respectively; 80.1% of risk was unexplained. Risk factors for severe deficits included age 5-9 years at diagnosis (OR 1.95, 95% CI 1.36-2.80), BMI&lt;18.5 kg/m 2 (OR 3.95, 95% CI 2.28-6.85), &gt;20Gy cranial radiotherapy (OR 5.22, 95% CI 3.74-7.30), testicular/pelvic radiation (OR 1.70, 95% CI 1.19-2.44), smoking (OR 1.71, 95% CI 1.21-2.43), and physical inactivity (OR 1.91, 95% CI 1.10-3.33). AFs were 10.9%, 7.0%, 2.9%, 11.5%, 6.7%, and 3.2% respectively; 57.8% of risk was unexplained. Those with deficits were less likely to live independently, to be employed, and more likely to require assistance with personal care needs (Table). Fracture risk was greatest among those with any BMD deficit, and mortality risk was greatest among those with severe deficits. Conclusions: Deficits in BMD among childhood cancer survivors are related not only to treatment, but also to modifiable health behaviors. In this population, children exposed to radiation or glucocorticoids are at greatest risk for poor bone quality and should be counselled to optimize health behaviors.[Table: see text]
Variant allelic fraction of driver mutations predicts success of genomic methylation classification in CNS tumors.
Authors: Pouya Jamshidi, Matthew McCord, Rimas Vincas Lukas, Lucas Santana-Santos, Lawrence Jennings, Craig M. Horbinski
Journal: Journal of Clinical Oncology (2022)

e14035 Background: Whole genome CpG DNA methylation profiling is proving to be an extremely valuable tool in the diagnostic and prognostic classification of central nervous system (CNS) tumors, and is especially adept at discriminating between very different tumors, or tumor subtypes, that are histologically similar. However, like any bulk assay, reliability of methylation-based classification depends on sufficient tumor cellularity, as admixed nonneoplastic elements (e.g., neurons, glial cells, inflammatory cells) have their own unique methylation profiles, and thus can skew the results. Currently, it is recommended that at least 70% of the analyzed specimen be tumor; however, this is based on subjective estimates from light microscopy. Many neoplastic entities have well-known driver mutations that occur in virtually 100% of tumor cells, and next-generation sequencing (NGS) assays can detect those mutations and report their relative amounts in the form of Variant Allelic Fraction (VAF). Since NGS and methylation profiling are now frequently being done on the same tumor block, we sought to determine whether driver mutation VAF affects the accuracy of methylation profiling, and whether VAF can help establish more rigorous cutoffs for quality assurance. Methods: Using NGS and Infinium Epic850K methylation arrays, we evaluated 62 CNS neoplasms representing a range of entities, including TERT promoter-mutant glioblastoma, IDH-mutant astrocytoma, IDH-mutant oligodendroglioma, SHH-driven medulloblastoma, and CTNNB1-driven adamantinomatous craniopharyngioma. Results: VAFs of each driver mutation ranged between 1-60%. Forty-four of 62 cases (71%) had a methylation classification score ≥0.9, the most widely accepted cutoff for a successful result. A fit-of-mixture analysis via CutoffFinder (PMID: 23251644) suggested that the optimal VAF cutoff is 21%. Forty-one of 46 (89%) cases with a VAF of 21% or higher had a methylation classification score ≥0.9, whereas only 3/16 (19%) at or below 21% were classifiable with methylation profiling ( P&lt; 0.0001 by Fisher’s exact test). Nonlinear regression of VAF versus methylation score by least squares fit produced R 2 = 0.54, with sum of squares = 2.0. Conclusions: These data indicate that VAF can serve as a useful predictor of classification success via methylation profiling, and should be taken into account when interpreting methylation profiling results.
Phase Ib study of anti-PD-L1 monoclonal antibody socazolimab in combination with nab-paclitaxel as first-line therapy for advanced urothelial carcinoma.
Authors: Rong Duan, Yixun Liu, Xuechun Hu, Chuanliang Cui, Lu Si, Xinan Sheng, Zhi Liu, Ping Xiang, Xieqiao Yan, Siming Li, Li Zhou, Juan Li, Yu Jie Li, Rachel Ng, Xiang Rong Dai, Benjamin Xiaoyi Li, Zhihong Chi, Jun Xiao, Jun Guo, Bixia Tang
Journal: Journal of Clinical Oncology (2022)

4563 Background: PD-1/PD-L1 immune checkpoint inhibitors (ICIs)0have demonstrated activity in the postplatinum and platinum-ineligible settings for advanced urothelial carcinoma (aUC). As only around 30% of patients with aUC can tolerate platinum standard treatment, first-line ICIs combined with non-platinum drugs have certain research value. Therefore we assessed the safety and efficacy of anti-PD-L1 monoclonal antibody Socazolimab in combination with nab-paclitaxel as first line therapy in aUC (NCT04603846). Methods: This is a multi-center,single-arm, phase Ib study which enrolled aUC patients with treatment-naive or first recurrence more than 6 months after the end of adjuvant chemotherapy in China. Eligible patients received Socazolimab (5mg/kg) and nab-paclitaxel (260mg/m 2 ) every 3 weeks. Primary endpoint was to investigate the safety and tolerability of nab-paclitaxel in combination with Socazolimab. Second endpoints were the objective response rate (ORR) and progression-free survival (PFS). Results: 20 patients were enrolled, including 5 renal pelvis urothelial carcinoma, 8 bladder urothelial carcinoma, and 7 ureteral carcinoma. The median age was 69 years. As of January 14, 2022, the median follow-up time was 5.49 months. Median number of treatment cycles was 6.5 cycles. No patients had dose limiting toxicity. Among the 17 patients who had received at least one tumor assessment, 8 patients achieved partial responses. ORR was 52.94% (95% CI, 27.81-77.02). DCR was 88.24% (95% CI, 63.56-98.54). Median PFS was 8.18 months (95% CI, 5.32-13.60). Adverse reactions related to the study drug were mainly Grade 1-2. Common adverse reactions included rash (6/20,30%), increased alanine aminotransferase (6/20, 30%), increased γ-glutamyltransferase (4/20, 20%),sinus bradycardia (4/20, 20%), increased aspartate aminotransferase (4/20, 20%),pruritus (3/20, 15%). Grade 3 or higher treatment-related adverse events occurred in 4 (20%) patients, mainly Grade 3 increases in alanine aminotransferase (2/20, 10%). No confirmed treatment-related deaths occurred, and no treatment-related deaths occurred, and no new safety signals were observed. Conclusions: Socazolimab combined with nab-paclitaxel as first-line treatment was effective and well-tolerated in Chinese patients with advanced urothelial carcinoma, warranting phase II trials. Clinical trial information: NCT04603846.
<sup>89</sup>Zirconium-labelled girentuximab (<sup>89</sup>Zr-TLX250) PET in patients with urothelial cancer (ZiPUP): A phase I trial of a novel staging modality for urothelial carcinoma.
Authors: Dickon Hayne, Richard Gauci, Mohammed Al-Zubaidi, Pravin Viswambaram, Steve P McCombie, Elizabeth Chien Hern Liow, Nat Lenzo, Thomas Ferguson, Paola Antonini, Danielle Meyrick, Colin Hayward, Andrew David Redfern
Journal: Journal of Clinical Oncology (2022)

TPS4609 Background: Bladder cancer is a lethal disease with a rising incidence. The current standard imaging modalities for staging are either CT of the chest, abdomen and pelvis or FDG PET/CT. However, there are issues with using these modalities for staging. CT is known to have relatively low sensitivity for detecting low volume metastatic disease, while FDG is predominantly renally excreted and therefore has intense activity in the urinary tract, which limits its utility to detect bladder or upper tract lesions, or nodal metastases in close proximity to the urinary tract. Zirconium-89-Girentuximab (89Zr-TLX250) may have utility in the accurate staging of bladder and urothelial cancer, with less renal excretion as compared to FDG, however this has not previously been investigated. ZipUp is an investigator initiated trial. South Metropolitan Health Service WA is the trial sponsor. The study received funding and study drug support from Telix Pharmaceuticals Methods: ZiPUP is a single-arm, phase I trial examining the feasibility, safety, and utility of 89Zr-TLX250 PET/CT in patients either undergoing pre-operative staging of urothelial carcinoma or bladder cancer for curative intent, or with known metastatic urothelial carcinoma or bladder cancer. All participants will undergo 89Zr-TLX250 PET/CT and will need to have undergone recent FDG PET/CT for means of comparison. This trial aims to recruit 10 participants undergoing staging and 10 participants with known metastatic disease. The primary endpoint is effectiveness by assessing sensitivity and specificity in detecting lymph node metastases compared to FDG PET/CT; secondary endpoints are safety, tolerability, and feasibility. The first patient was enrolled in this single site study and the study is expected to be completed by December 2022. If 89Zr-TLX250 PET/CT is proven to be feasible, safe, and effective in staging urothelial cancer, it could improve the appropriate selection of treatment for patients with metastatic or primary urothelial carcinoma or bladder cancer. Clinical trial information: NCT05046665.
Real-world treatment outcomes and healthcare resource use associated with antiemetics among cancer patients on highly emetogenic platinum-based chemotherapy.
Authors: Rudolph M. Navari, Winnie Nelson, James K Utt, Sofia Shoaib-Agwan, Risho Singh, Weiping Zhang, William L. Bailey
Journal: Journal of Clinical Oncology (2022)

e24109 Background: Chemotherapy-induced nausea and vomiting (CINV) is a recognized adverse outcome among cancer patients, and guidelines recommend appropriate prophylactic antiemetics. Highly emetogenic chemotherapy (HEC) is associated with high risk of CINV that potentially lead to additional healthcare resource use. This retrospective study aimed to quantify the treatment outcomes and resource utilization associated with antiemetic use to prevent CINV in a broad US population. Methods: Cancer patients who received platinum–based HEC were identified in the All Payers Claims Database (APCD). The APCD is a database representing the US population with commercial, Medicare, or Medicaid insurance. Insurance claims denote medical care associated with payment, providing an optimal data source to study healthcare resource use. Study patients were age ≥18 years and administered IV 1) fosnetupitant/palonosetron (IV NEPA), 2) aprepitant/fosaprepitant + palonosetron (IV APPA) or 3) aprepitant/fosaprepitant + ondansetron (IV APON) along with HEC. Patients were identified from 1/2016 - 12/2019. The index date was the first treatment date of a study antiemetic. Demographic and clinical characteristics were evaluated in the baseline period, which was 12 months prior to the index date. The post-HEC follow-up period was 14 days, starting the day after each HEC administration. Outcomes were reported descriptively as weighted means, with the cycles of treatment as the unit of analysis, including nausea &amp; vomiting, dehydration, fluid-electrolyte imbalances, and hydration therapy. Results: Study included 1,216 IV NEPA, 43,537 IV APPA, and 16,140 IV APON patients who received HEC. During the post-HEC follow-up period, IV NEPA patients reported fewer occurrences of nausea &amp; vomiting and fluid-electrolyte imbalances per cycle of treatment when compared to IV APPA and IV APON patients. Despite having similar or more dehydration claims for IV NEPA, the occurrence of hydration therapy was lower or similar to the other study groups. (Table). Conclusions: The choice of antiemetics to prevent CINV among cancer patients receiving HEC may impact real-world outcomes and healthcare resource use.[Table: see text]
The prevalence of HPV infection in Chinese solid tumor patients.
Authors: Cheng Yang, Yizhou Wang, Ming Liu, Tanxiao Huang, Wenting Liao, Yingmei Li, Tianhao Mu, Shifu Chen
Journal: Journal of Clinical Oncology (2022)

e22519 Background: Human papillomavirus (HPV) is a family of small double-stranded DNA viruses. It is associated with a series of cancer types, such as cervical, oropharyngeal, anal, vulvar, vaginal, and penile cancers. In the world, nearly 70% of HPV-related cancer cases are HPV types 16 and 18. In this study, we investigated HPV infection prevalence among a cohort of Chinese solid tumor patients. Methods: The study enrolled thousands of Chinese patients with different types of cancers. We finally collected 4,606 tumor tissue DNA (ttDNA), 7,296 plasma cell-free DNA (cfDNA), and 7,509 peripheral blood mononuclear cell genomic DNA (gDNA) samples, respectively. Using a targeted capture technique that covering the whole reference genome of HPV16 and HPV18 and the next generation sequencing (NGS) technology, we calculated the percentage of HPV16 and HPV 18 reads in all sequencing reads for each sample. Finally, we explored the prevalence of HPV infection in each cancer type. Results: Based on different types of DNA samples, the HPV infection rate was 38.75%, 28.62%, and 10.43% in ttDNA, cfDNA, and gDNA samples, respectively. Besides, the magnitudes of the mean percentage of HPV reads in all the sequencing reads in ttDNA, cfDNA and gDNA samples were 10 -5 , 10 -6 and 10 -8 , respectively, while in the HPV infection positive the percentages of ttDNA, cfDNA, and gDNA samples increased to 10 -4 , 10 -5 , and 10 -7 , respectively. The prevalence of HPV infection rate in different cancer types was shown in table. Conclusions: ttDNA and cfDNA are better material for HPV infective detection compared with gDNA, and NGS is capable of HPV detection.[Table: see text]
The impact of face-to-face evaluation in the clinical assessment of cancer patients.
Authors: Mirella Stival, Pedro Nazareth Aguiar, Marcos Aurelio Fonseca Magalhaes Filho, Auro Del Giglio
Journal: Journal of Clinical Oncology (2022)

e13651 Background: Despite the growing popularity of teleoncology in the context of the COVID-19 pandemic, there is great concern about the quality and accuracy of clinical encounters as there is virtually no physical examination (PE) provided. Objectives: To evaluate the primary sites and clinical variables that could predict a higher frequency of abnormal PE findings and a consequent change in conduct, thus allowing the selection of patients who are possibly ineligible for remote care. Methods: Observational and prospective study, conducted at the oncology center of two public hospitals in Brazil. A multiple-choice form, developed by the researchers, was filled in to collect the clinical variables of the patients, data regarding the service, and oncological conduct determined at the end of the consultation. Results: 368 clinical evaluations of patients with cancer were included in the study, with breast, colorectal, and prostate tumors being the most frequent. The physical examination was normal or with alterations already seen in previous consultations in 87% of the cases while 13% had new changes in the PE. Among patients with new changes in the PE, cancer treatment was maintained in 59% of cases. Thus, PE led to a change in antineoplastic therapy in 12 cases (3% of all patients being 1% only because of the PE findings and 2% after completion of a complimentary examination). Statistical analysis showed a significant association between the altered PE and the following variables: primary site breast (n=27; 21%; p&lt;0.01), head and neck (n=7; 26%; p&lt;0, 01) and ovary (n=2; 17%; p&lt;0.01), presence of symptoms (n=31; 21%; p&lt;0.01), and treatment with palliative intent (n=23; 19%; p&lt;0.01). However, only the presence of symptoms showed a positive association with the altered PE and consequent treatment change (p&lt;0.01). Conclusions: Telemedicine seems to be a safe modality in the vast majority of cases, given the large percentage of asymptomatic patients with no changes in the PE during face-to-face care. Regarding symptomatic patients, we suggest priority to in-person care. In those with EC IV tumors undergoing palliative treatment or with breast, head and neck, and ovarian cancer, we recommend evaluating case by case and considering face-to-face care.
Effects of liver metastases on efficacy of immune checkpoint blockade in treatment refractory, metastatic colorectal cancer (CRC): CCTG CO.26.
Authors: Eric Xueyu Chen, Jonathan M. Loree, Dongsheng Tu, Christopher J. O'Callaghan, Hagen Fritz Kennecke, Derek J. Jonker, Ahmad Chaudhary, Bruce Colwell, Mohammed Harb, Nathalie Aucoin, Felix Couture, Setareh Samimi, Petr Kavan, Francine Aubin, Benoit Samson, John R. Goffin, Scott Berry, Tahir Abbas, Sheryl L. Koski, Alice Chia-chi Wei
Journal: Journal of Clinical Oncology (2022)

3600 Background: Immune checkpoint blockade has limited activity in microsatellite-stable (MSS) or mis-match repair proficient (pMMR) CRC. Recent findings suggest that immunotherapy efficacy may be modulated by the presence of liver metastases. We conducted a retrospective analysis of the Canadian Cancer Trials Group (CCTG) CO.26 study to investigate the relationship between the presence of liver metastases and activity of immune checkpoint blockade. Methods: The CCTG CO.26 study was a randomized phase II study (NCT02870920). Pts with treatment refractory CRC were randomized to durvalumab, tremelimumab and best supportive care (BSC) or BSC alone in a 2:1 fashion. Treatment consisted of durvalumab (1500 mg) q 28 days and tremelimumab (75 mg) q 28 days for the first 4 cycles. The primary endpoint was overall survival (OS) and a two-sided p-value &lt;0.10 was considered significant. Results: Between 08/20106-06/2017, 180 pts were enrolled and 179 treated as randomized. Pt baseline characteristics were balanced between groups. With a median follow-up of 15.2 months, the median OS was 6.6 months for durvalumab and tremelimumab and 4.1 months for BSC (p = 0.07; Hazard ratio (HR): 0.72, 90% confidence interval (CI): 0.54 – 0.97). Progression free survival (PFS) was 1.8 months and 1.9 months respectively (HR 1.01, 90% CI: 0.76 – 1.34). Disease control rate (DCR) was 22.6% for durvalumab and tremelimumab and 6.6% for BSC (p = 0.006). At study entry, liver metastases were absent in 29.4% pts. Pts without liver metastases had improved OS compared to those with liver metastases, irrespective of treatments. PFS was significantly longer in those without liver metastases on durvalumab and tremelimumab (HR: 0.55, 90% CI: 0.31 – 0.97, p = 0.08, interaction p = 0.02). DCR was 49% in patients without liver metastases with durvalumab and tremelimumab, compared to 10% in those with liver metastases (Odds Ratio: 0.12, 90% CI: 0.05 – 0.26). Conclusions: Pts without liver metastases had improved OS and PFS, and higher DCR. Absence of liver metastases may be an indicator for improved efficacy of immune checkpoint blockade and should be investigated in future studies. [Table: see text]